Abstract

The intestinal epithelium is in direct contact with a vast microbiota, yet little is known about how epithelial cells defend the host against the heavy bacterial load. To address this question we studied Paneth cells, a key small intestinal epithelial lineage. We found that Paneth cells directly sense enteric bacteria through cell-autonomous MyD88-dependent toll-like receptor (TLR) activation, triggering expression of multiple antimicrobial factors. Paneth cells were essential for controlling intestinal barrier penetration by commensal and pathogenic bacteria. Furthermore, Paneth cell-intrinsic MyD88 signaling limited bacterial penetration of host tissues, revealing a role for epithelial MyD88 in maintaining intestinal homeostasis. Our findings establish that gut epithelia actively sense enteric bacteria and play an essential role in maintaining host-microbial homeostasis at the mucosal interface.

Model of small intestinal Paneth cell function. We have shown that Paneth cells directly sense enteric bacteria through cell-autonomous MyD88 activation and limit bacterial penetration of the mucosal surface. MyD88-dependent sensing triggers expression of a complex antimicrobial program that could function to limit the numbers of bacteria that localize at the mucosal surface, in or beneath the mucus layer. This would in turn limit the numbers of bacteria that are translocated to mesenteric lymph nodes (MLN) via dendritic cells (DCs). In the same way, Paneth cells could inhibit pathogen access to surface niches, thus accounting for the essential role of Paneth cells in limiting mucosal penetration and dissemination of Salmonella.